Vascular integrity is key to normal function of the organism. While much has recently been learned about factors controlling new vessel growth, maintenance of vascular integrity remains poorly understood. In the previous grant cycle we have demonstrated that FGF signaling plays a key role in maintenance of endothelial cell contacts and that disruption of this signaling leads to disintegration of the mature vasculature. Thus, FGFs appear to play a major, and a totally unexpected, role in this process. In this grant, therefore, we propose to 1) Determine which FGF receptors are involved 2) How this action is achieved. The thorough molecular understanding of this process will likely provide new tools for treatment of vascular diseases, and, potentially, cancer. PUBLIC HEALTH RELEVANCE: In this grant, therefore, we propose to 1) Determine which FGF receptors are involved 2) How this action is achieved. The thorough molecular understanding of this process will likely provide new tools for treatment of vascular diseases, and, potentially, cancer.